DE60113410T2 - SYRINGE SYSTEMS FOR LYOPHILIZED MEDICAMENTS AND METHOD FOR THE PRODUCTION THEREOF - Google Patents

Abstract

A syringe system requires a decreased vertical travel for sealing during a lyophilization process and therefore provides for increased utilization of space in a lyophilization chamber. The syringe system is provided with a sterility maintenance sleeve including a stopper affixed thereto for sealingly engaging the syringe barrel to define a drug chamber. The sterility maintenance sleeve is provided with a venting passage to permit egress of vapor from the drug chamber during lyophilization. A plug cap cooperating with the sterility maintenance sleeve includes an occluding tip which is adapted to occupy the venting passage and seal the drug chamber after lyophilization. The plug cap is provided with a support structure in the form of flexible fins for supporting the plug cap in a venting position in which the occluding tip is removed from the venting passage to permit egress of drug solution vapor from the drug chamber during lyophilization. After lyophilization, the plug cap is moved into a sealing position in which the drug chamber is sealed against contamination.

Description

technical area

The This invention relates generally to syringe systems suitable for packaging, Mixing and dispensing a medical solution are suitable and trained are by adding a dry, lyophilized drug ingredient with a liquid thinner is mixed. More particularly, the invention relates to syringe systems, which allow the lyophilization of a drug solution contained therein. The invention also relates to methods of making these syringe systems.

background the invention

in the In general, lyophilization is a volatile component process such as water-containing solvents from a substance be removed. Certain substances, especially pharmaceutical substances, are about longer Time more stable, if the fleeting Components are removed. Since lyophilized drugs are usually more stable, a longer one Shelf Life have, a more reliable Have purity and are easier to store and transport than other formulations, was the lyophilization in the pharmaceutical Industry something everyday.

It is known, "wet / dry" Arnzeimittelmisch- and dispensing products containing a primary syringe system, containing a lyophilized drug and a secondary syringe system use a diluent contains to to recover the lyophilized drug. If the drug to be administered to a patient becomes the secondary syringe system in the primary Syringe system inserted and the diluent in the primary syringe barrel scattered to recover the lyophilized drug. These "wet / dry" syringe systems are advantageous in pharmaceutical applications in which premixed Solutions or Suspensions of a drug are not stable enough to withstand longer storage periods. Such systems are disclosed in U.S. Patent No. 5,779,668.

Usually, the manufacture of the primary syringe system containing the lyophilized drug involves bulk processing of a series of syringe systems in a lyophilization chamber. Prior art lyophilization chambers are disclosed in U.S. Patent Nos. 5,178,074; 1 and exemplified in U.S. Patent No. 4,506,455. The lyophilization chamber 10 generally comprises a chamber wall 12 which is prepared to provide isolation during the lyophilization process. In the wall 12 are a bunch of subjects 14 enclosed, which are adapted to move in relation to each other, and include the devices such as cooling and heating coils for raising and lowering the compartment temperature. A hydraulic actuator 18 moves the upper tray up, creating a space between the upper tray and the adjacent second tray, and a number of syringe systems 22 on trays or "rolls" 20 are loaded on the second compartment. The containers or trays 20 are usually on a promotion cart 26 transports and slides across a loading table 24 along, leaving the trays on the respective compartments 14 can be loaded. The upper compartment and the second compartment are then lifted and the syringe systems 22 loaded on the third compartment. This loading sequence is repeated until the vertical syringe systems 22 the spaces between the subjects 14 occupy. Once fully loaded, the chamber door becomes 19 closed and the interior subjected to a lyophilization process, which usually takes several days to complete. After the lyophilization process is completed, the upper tray is lowered and the trays are compressed so that the movement of the trays causes collapse, in a manner that will be described below.

typical Lyophilization procedures include two stages. In the first Stage becomes the drug solution low temperatures, for usually -50 ° C, exposed and completely frozen, around the water or the other solvent from the solution components to separate. In the second stage, the water or other solvent under carefully controlled conditions and under a high vacuum by the slow Heat the contents of the frozen product separated, leaving the solvent leaves the products by sublimation. The drying is fulfilled, if the frozen solvent is converted into steam. This steam wanders through the crystallized Medicines and escapes through a bleeding system from the syringe system.

The 2 and 3 illustrate a prior art syringe system as disclosed in US-5779668 to allow venting of the drug during lyophilization. During the lyophilization process, the syringe system becomes 30 held in a vertical position in a metal holder or in a roller (not shown). 2 illustrates the syringe system constructed in a ventilation position 30 , The syringe system 30 includes a generally cylindrical syringe barrel 32 who has an open end 33 and a closed end 34 includes. The closed end 34 closes a delivery passage 36 one, later for the delivery of the mixed drug from the syringe system 30 is used. During lyophilization, the delivery passage becomes 36 from a lock 37 sealed, and the syringe barrel 32 contains a drug solution 35 ,

In accordance with the prior art syringe systems, venting is accomplished through a series of ventilation channels 39 provided in the syringe barrel 32 near the open end 33 are formed. These channels are between a series of ribs 37 formed integral with the syringe barrel 32 are shaped. The syringe system 30 also includes a sterility maintenance cuff 42 and a slip-on cap 56 a, which are provided to the interior of the syringe barrel 32 to protect against contamination when the syringe once, as in 3 shown, is moved to its sealed position. The sterility maintenance cuff 42 closes a section 52 a large diameter, from which a stopper holding head 50 which is shaped to elastically rubber stopper thereon 44 to keep. The stopper 44 is formed around the inner surface of the syringe 32 sealingly intervene, and poke in like in the 2 shown ventilation position against the ribs 37 , whereby the escape of vapor from the drug chamber 45 the syringe 32 through the channels 39 is allowed.

3 illustrates the syringe system 30 which is constructed in a sealing position after the lyophilization process has been performed. The sterility maintenance cuff 42 and the slip-on cap 56 are moved to the sealing position in which the plug 44 continue in the syringe 32 located, and a sealing head 57 the slip-on cap 56 take the syringe. As will be appreciated by one of ordinary skill in the art, the slip-on cap and sterility preservation cuff will become 42 moved by the movement of the compartments in the Lyophilisierungskammer from the ventilation position in the sealing position.

The Document US-5435076 discloses a device for an injection device, the one Injection cartridge includes a drug solution and a cylindrical cuff carries with it, a front end closure Has. The cartridge has a front opening that allows that evaporated solvents the drug solution while the lyophilization process escapes from the cartridge. After this The lyophilization process is completed, the cartridge sealed by the cuff lock, which in the front opening of the Cartridge penetrates to close it sealingly.

syringe systems require from the prior art a rather extensive vertical path of the sealing components, when they are out of a ventilation position move to a sealing position. These path lengths limit performance the Lyophilisierungskammer a, since the subjects arranged with intervals Need to become, to accommodate the syringe system when in the ventilation position is constructed. Because the lyophilization process for some pharmaceutical substances can take several days, is the space in the Lyophilisierungskammer - usually one very expensive part of the equipment - a luxury. It would be accordingly desirable, to provide a syringe system that is superior to the syringe systems the prior art, a lower vertical movement for the sealing requires. Such a system would the more efficient use of the space in the lyophilization chamber allow.

The ventilation techniques The syringe systems of the prior art are also disadvantageous since they do not have an effective flow path for the Drug solution vapor while provide the drying steps of the lyophilization. More accurate is the fluid path the steam must travel to during the Lyophilizing from the drug chamber to escape to the environment a bit limited, because the ventilation passages through the engagement of an elastic plug with those in the syringe barrel trained channels be formed. It would be therefore desirable to provide a syringe system that during the lyophilization a effective flow path for the Provides drug solution vapors, which makes the time while of lyophilization for drying is required is reduced.

Summary of the invention

The The benefits and advantages described above are provided by the present invention Invention, which provides a syringe system according to claim 1, the a smaller vertical distance is needed if it is from a ventilation system changes to the sealing structure. The sterility maintenance cuff can initially placed in an installed location, with the plug, as compared with the prior art devices is arranged in the syringe barrel and thus the overall height of the syringe system in the ventilation system reduced.

One Another aspect of the invention is a method. for manufacturing A syringe system according to claim 11.

The occluding tip is preferably constructed to allow the proper vapor flow through the vent passage for effective drying during the lyophilization process. More precisely, the closing tip becomes provided with a tapered end dimensioned to provide an annular flow passage with the vent passageway formed in the sterility maintenance sleeve. The occluding tip is configured to occupy, in the venting position, an enlarged diameter vent passage portion such as a female threaded portion for later receiving an externally threaded portion of a diluent syringe. The shape of the flow passage for vapors from the drug solution is therefore less limited than in prior art devices, thus providing more efficient and faster lyophilization.

The Aufsteckkappe is preferably flexible with a Stutzaufbau in the form Provided ribs extending from a central section Outside extend. The ribs work to fit into an inner surface of the Sterility maintenance sleeve frictionally to engage so that the Aufsteckkappe is supported in the ventilation position. The ribs are flexible enough to deform and thereby to allow the slip-on cap at the application of a Force on the cap inside the sterility maintenance cuff moved without the movement of the sterility maintenance cuff in the syringe barrel to effect. The ribs provide in conjunction with the inner surface of the Sterility maintenance sleeve also great Flow passages for the drug solution vapor ready, while Lyophilizing a more effective dry and a more effective Steam exit is provided from the drug chamber.

numerous Further advantages and features of the present invention will be readily apparent from the following detailed description of the invention, from the claims and from the accompanying drawings.

Short description of drawings

In the accompanying drawings which form a part of the specification and in which same ziffers are used to make equal parts to mark in the same is

1 a schematic diagram of a Lyophilisierungskammer and a charger according to the prior art as described above;

2 a sectional view of a syringe system of the prior art in a ventilation position as described above;

3 a sectional view of a syringe system of the prior art in a sealed position as described above;

4 a sectional view of an assembled exemplary syringe system according to a preferred embodiment of the present invention;

5 a sectional view illustrating a roller and a cylinder subassembly of an exemplary syringe system according to the invention;

6 a sectional view, the substructure of 5 and illustrates an added exemplary sterility cuff in accordance with the present invention;

7 a sectional view, the substructure of 6 and Figure 5 illustrates an added exemplary slip cap disposed in an evacuation position according to the present invention;

7a a cross-sectional view, with respect to the line 7a-7a in 7 is made;

8th a sectional view showing the structure 7 with the cap moved to a sealed position according to the present invention; and

8a an enlarged view in relation to the area 8a in 8th is done.

Detailed description the preferred embodiment

Even though this invention for an embodiment multiple forms accessible discloses this description and the accompanying drawings as examples of the invention only a few specific forms. It is not intended to limit the invention to the embodiments thus described. On The scope of the invention is indicated in the appended claims. Figures that the device represent some mechanical elements that are known and recognized by one skilled in the art. The detailed Descriptions of these elements are not required for an understanding of the invention and are accordingly presented herein only to the extent that necessary, for an understanding of novel features of the present invention to facilitate.

If you take it up now 4 Reference is made to an exemplary mounted syringe system according to the invention. The syringe system, generally with the numeral 100 Referring to Figure 1, a primary syringe barrel is included 102 one, the one open end 104 and opposite the open end 104 a closed end 106 Has. The GE closed end 106 closes a delivery passage 108 for the subsequent delivery of the mixed drug from the syringe barrel 102 to allow. A clasp 110 is provided in the delivery passageway to seal the interior of the syringe during the lyophilization process. The syringe system 100 also includes a sterility maintenance cuff 120 one to the syringe barrel 102 to seal against the contamination after the lyophilization process is completed. The sterility maintenance cuff 120 closes a generally cylindrical sleeve cylinder 123 a, which turns into a round stopper head 126 extends to a cylindrical plug 128 elastic to keep it. The stopper 128 and the closed end 106 the syringe barrel 102 determine a drug chamber 131 containing a lyophilized drug 170 contains. The sterility maintenance cuff 120 also includes a female thread section 124 to receive a male threaded fitting on a diluent syringe (not shown) to mix the lyophilized drug with a patient just prior to delivery.

A ventilation passage 130 extends within the sterility maintenance cuff 120 and through the plug holding head 126 and the female threaded portion 124 to the interior 125 of the sleeve cylinder 123 , The ventilation passage 131 also includes a generally circular plug passage 132 one in the stopper 128 trained and with the section of the ventilation passage 131 aligned through the plug holding head 126 extends.

A slip-on cap 150 is in the cuff cylinder 123 the sterility maintenance cuff 120 arranged to the syringe system 100 seal. The slip cap closes a generally cylindrical central portion 154 , a lid section 152 for sealing the open end 104 the syringe barrel 102 and a closing tip 156 one, extending from the middle section 154 extends. The closing tip 156 occupies and seals the vent passage in a manner that will be explained in more detail below. The lid section 152 the slip-on cap 150 is trained to open the end 104 to seal the syringe barrel and a shrink band 168 take. An annular sealing surface 182 is on a flange 183 provided in a syringe barrel 102 trained shoulder 184 intervenes. The shrink band will wrap around the flange 183 and shoulder 184 attached to the slip-on cap 150 on the syringe barrel 102 to moor and seal.

An exemplary method of manufacturing a syringe system according to the invention will now be described with reference to FIGS 5 - 8th described. 5 illustrates a subassembly of an exemplary syringe system according to the invention. The syringe barrel 102 that's the delivery passage 108 sealing closure 110 includes, contains the drug solution 112 and becomes, as known in the art, in a holder or a roll 103 provided to the syringe barrel 102 in a vertical position on the compartment of the lyophilization chamber. The role 103 is preferably made of a metal material such as aluminum, which is suitable for the heat conduction and in the heat conduction to the drug solution 112 and from it is suitable. The primary syringe barrel 102 closes several guide projections 114 one close to the open end 104 and integral with the syringe barrel 102 are formed. The guide projections 114 As will be explained, to support the sterility maintenance collar during installation. The guide projections 114 also work to rotate the sterility maintenance sleeve during installation and during later use of the syringe system 100 with a diluent syringe to recover the lyophilized drug. The guide projections 114 are preferably constructed to be of different lengths.

6 illustrates a step of providing the sterility maintenance sleeve 120 in the above with reference to 5 described substructure. The sterility maintenance cuff 120 is shown in an installed position in the syringe barrel as shown 102 inserted. The sterility maintenance cuff 120 closes a series of radially projecting tabs 136 a, extending from the cuff cylinder 123 extend to the outside. The projecting tabs 136 also extend in an angular vertical direction from the sleeve cylinder 123 path. The projecting tabs 136 work to keep the sterility maintenance cuff in place when the projecting tabs 136 on the tops of the shorter guide tabs 114 lie and between the longer guide projections 114 are arranged. The projecting tabs 136 Also work to prevent the sterility-maintaining cuff 120 with respect to the syringe barrel 102 rotates, especially if the diluent syringe later by using the female threaded connector 124 and an associated male threaded fitting on the diluent syringe (not shown) on the syringe system 100 is connected. In addition, the projecting tabs 136 designed to be elastic or to bend, or they can be fragile with the cuff cylinder 123 be connected to allow the sterility maintenance cuff to continue down in the syringe barrel 102 is plugged, as is for the stopper 128 necessary to later displace and redistribute the decayed drug.

Note that the projecting tabs 136 the guide projections 114 due to the different lengths of the projections 114 at various points on the inside of the sleeve cylinder 123 intervene along. This ensures that the force needed to start the sleeve cylinder 123 inside the syringe barrel 102 to collapse, is reduced.

As shown in this exemplary embodiment, the plug is located 128 approximately two-thirds in the depth of the syringe barrel 102 if the sterility maintenance cuff is 120 located in the installed position in which the sterility maintenance cuff 102 including its upper end 137 passing through the ends of the projecting tabs 136 is determined completely within the syringe barrel 102 is arranged. However, those skilled in the art will recognize that the exact position of the plug is dependent on the amount of syringe barrel 102 containing drug solution when the sterility maintenance cuff 102 in the installed position. The stopper 128 sealingly engages an inner surface of the syringe barrel 102 one. Preferably, the sleeve cylinder 123 the sterility maintenance cuff 120 Measure to a firm seal against the inner surface of the syringe barrel 102 to provide and yet the reciprocating within the syringe barrel 102 and in terms of allowing it, when the syringe system 100 is later used with a diluent syringe to reconstitute the lyophilized drug.

In accordance with a primary aspect of the invention, the sterility maintenance sleeve becomes 120 with a ventilation passage 130 provided with a generally circular cross-section extending through the female threaded portion 124 and the plug holding head 126 extends and the one at the stopper 128 formed stopper passage 132 includes. The ventilation passage 130 allows the escape of drug solution vapors during the lyophilization stage in the drug chamber 131 be generated. As will be appreciated by one of ordinary skill in the art, unlike the prior art syringe systems, venting is accomplished with the sterility maintenance cuff in the art 6 shown instal lated position allowed.

7 illustrates a step for inserting a slip cap 150 into the sterility maintenance cuff 120 according to the invention. Before inserting the syringe system 100 into the Lyophilisierungskammer is the Aufsteckkappe 150 as shown at a ventilation position in the sleeve cylinder 123 connected to the venting and the subsequent sealing of the syringe system 100 to allow. The slip-on cap 150 closes a generally cylindrical cover portion 152 , a generally cylindrical middle section 154 and a closing tip 156 one. The closing tip 156 is designed to be in the ventilation passage 130 to fit so that the fluid passage therein prevents and thereby the drug chamber 131 sealed against contamination. The closing tip 156 is generally cylindrical and includes a tapered tip 155 one that works initially to the occlusive tip 156 to lead into the ventilation passage and one at the stopper 128 formed elastic lip seal 129 intervene.

According to a further primary aspect of the invention, the slip cap 150 with a support structure 157 provided to support the Aufsteckkappe in the ventilation position. In a preferred embodiment, the support structure is in the form of four flexible projecting ribs 160 provided, extending from the middle section 154 the slip-on cap 150 extend outward (only two ribs are in 7 shown). If you take on additionally 7a Reference having a cross section with respect to the line 7a-7a in 7 represents, the projecting ribs extend 160 preferably in a non-radial direction from the center axis of the slip cap 150 to facilitate bending or deformation when the slip cap 150 in the cuff cylinder 150 is plugged. The support structure 157 supports the slip-on cap 150 in the ventilation position when the ribs 160 in an inner surface 121 of the sleeve cylinder 123 engage frictionally. Ribs 160 Make gaps filling passages 161 with the inner surface 121 of the sleeve cylinder 123 to the escape of the drug solution vapors from the interior of the sleeve cylinder 123 to the environment of the syringe system 100 to allow.

According to another primary aspect of the invention, the occlusive tip becomes 156 the slip-on cap 150 just inside the enlarged section 138 of the ventilation passage 130 in the female thread section 124 used when the slip cap 150 in the ventilation position. In this way, as will be appreciated by those skilled in the art, the occlusive tip will 156 and the inner surface of the female threaded portion 124 a generally annular flow passage is formed. Moreover, the size of the annular passage is such that the flow area is equal to or greater than the flow area of the passage through the plug holding head 126 is provided to allow for the escape of steam the drug chamber 131 to provide a non-limited flow path (P). In a similar way, that puts between the ribs 160 the slip-on cap 150 and the sleeve cylinder 123 provided flow path has a flow area equal to or greater than the flow area between the occluding tip 156 and the female threaded portion 124 to provide unrestricted vapor escape and drying during the lyophilization process.

In accordance with another aspect of the invention, the lid portion 152 the slip-on cap 150 with a structure for sealing the open end 104 the syringe barrel 102 provided. More specifically, in this exemplary embodiment, the lid portion 152 with an annular protruding lip 162 provided, extending in an axial direction from the lid portion 152 extends and an annular incision 164 forms around the top of the syringe barrel 102 formed lip 172 take. In accordance with the advantageous aspects of the present invention, the vertical height of the syringe system installed in the vent manifold becomes 100 reduced compared to the prior art. Unlike prior art devices, the plug must 128 not at the top of the syringe barrel 102 be aligned so that the venting takes place. Rather, the stopper and the sterility maintenance cuff can 120 be aligned in the installed position and yet the ventilation of the drug chamber 131 allow.

8th illustrates a step for sealing the ventilation passage 130 by the movement of the slip cap 150 in a sealing position. As will be appreciated, the movement of the slip cap 150 usually in response to the movement of the compartments in the lyophilization chamber. In the sealing position becomes the occluding tip 156 in the ventilation passage 130 arranged. In accordance with another aspect of the invention, a lip seal 129 at the stopper 128 provided to the outer surface of the occluding tip 156 sealingly intervene. Preferably, the plug passage 132 so great that the introduction of the occlusive tip 156 in the stopper passage 132 for outward deformation of the plug passage 132 leads, leaving the lip seal 129 against the closing tip 156 is biased. It will also be appreciated that the presence of the occlusive tip 156 in the ventilation passage 130 keeps the ventilation passage in a free state; ie the migration of the lyophilized drug 170 in the ventilation passage 130 where it might cause interference between a later inserted diluent syringe (not shown) is prevented.

If the slip cap 150 in the in 8th shown sealing position moves, represents the occlusive tip 156 a seal with the plug passage 132 ready to use the lyophilized drug 171 to seal in the chamber. In addition, the lid section 152 the slip-on cap 150 an additional seal ready when the annular, protruding lip 162 the lid portion in the open end 104 the syringe barrel extends and the lip 172 the syringe barrel 102 in the annular incision 164 occurs. Furthermore, between the sealing surface 182 on the lid section 152 and the shoulder 184 on the syringe barrel 102 provided an additional seal. Finally, from the shrink band 184 ( 4 ) around the annular shoulder 184 and the flange 183 attached, provided an additional seal. Thus, it will be appreciated that the exemplary syringe system according to the present invention has at least four seal interfaces against contamination of the lyophilized drug 170 provides.

Of the One of ordinary skill in the art will recognize that the present invention Invention provides a syringe system that in a ventilation position can be constructed by a smaller vertical dimension, as previously possible in the prior art is characterized. In a normal example is for Syringe systems for the administration of 1 to 3 cubic centimeters of a drug are suitable, the distance required to move the Aufsteckkappe from the ventilation position in a sealing position no longer than about 5/8 inches. This is in contrast to prior art devices, those for syringe systems a similar one Performance for usually more than a one-inch distance required. In this way, lyophilization chambers, which are constructed to be with syringe systems according to the present invention to work with subjects be provided, which are closer to each other, which is why the subjects closer to the lyophilization chamber can lie against each other and the performance of the chamber itself can be increased, so they A larger number to accommodate syringe systems than in the prior art possible was.

you It will also be appreciated that the invention is more effective and less restricted flow for the Steam outlet provides as systems of the prior art. thus can the time span for the drying stage of the lyophilization process is required is shortened become.

Out the previous detailed description of the invention and its Illustrations will be apparent that numerous changes and modifications performed can be without departing from the scope of the appended claims.

Claims (14)

A syringe system ( 100 ) for containing a lyophilized drug, the syringe system comprising: a syringe barrel ( 102 ), which has an open end ( 104 ) and an opposite output end ( 106 ) includes; a sterility maintenance cuff ( 120 ) in the syringe barrel ( 102 ) and a sleeve cylinder ( 123 ), which has an interior ( 125 ), wherein the sterility maintenance cuff ( 120 ) a plug attached thereto ( 128 containing the sterility maintenance cuff ( 120 ) can be moved and the sealing in the syringe barrel ( 102 ) engages a drug chamber ( 131 ) for containing the drug solution ( 170 ) to determine; characterized in that the syringe system comprises a ventilation passage ( 130 ) in the sterility maintenance cuff ( 120 ) through the plug ( 128 ) to prevent the escape of the drug solution vapor from the drug chamber ( 131 ) in the interior ( 125 ) of the sleeve cylinder ( 123 ), when the syringe system ( 100 ) is subjected to a lyophilization process; and a slip-on cap ( 150 ) cooperating with the sterility maintenance cuff ( 120 ) and within the sterility maintenance cuff ( 120 ) from a ventilation position, in which the steam outlet from the drug chamber ( 131 ) in the interior ( 125 ) during the lyophilization process through the ventilation passage ( 130 ) can be moved to a sealing position in which the fluid communication between the drug chamber ( 131 ) and the interior ( 125 ) is prevented by the Aufsteckkappe ( 150 ) in the ventilation passage ( 130 ), whereby the drug chamber ( 131 ) is sealed. The syringe system of claim 1, wherein the sterility maintenance sleeve ( 120 ) further comprises a plug holding head ( 126 ) to the stopper ( 128 ), whereby the ventilation passage ( 130 ) through the plug holding head ( 126 ). The syringe system of claim 1, wherein the ventilation passageway ( 130 ) one in the stopper ( 128 ) stopper passage ( 132 ). The syringe system according to claim 1, wherein the push-on cap ( 150 ) a closing tip ( 156 ) for insertion into the ventilation passage ( 130 ). The syringe system of claim 4, wherein the occlusive syringe ( 156 ) a tapered surface ( 155 ). The syringe system according to claim 4, wherein the ventilation passageway ( 130 ) one in the stopper ( 128 ) formed stopper passage ( 132 ) and one at the stopper ( 128 ) formed sealing lip ( 129 ), wherein the sealing lip ( 129 ) is designed to penetrate into the occluding tip ( 156 ) sealingly intervene. The syringe system according to claim 4, wherein the cap ( 150 ) a support structure ( 157 ) to the cap ( 150 ) in the ventilation position. The syringe system of claim 7, wherein the support structure ( 157 ) a variety of ribs ( 160 ), which extends from a middle section of the slip-on cap ( 150 ) extend to the outside in the sleeve cylinder ( 123 ) of the sterility maintenance cuff ( 120 ) intervene. The syringe system according to claim 1, wherein the syringe barrel ( 102 ) around the open end ( 104 ) around a lip ( 172 ) and wherein the slip cap ( 150 ) further comprises an annular recess ( 164 ) into the lip ( 172 ) sealingly intervene. The syringe system according to claim 1, wherein the push-on cap ( 150 ) is adapted to move relative to the sterility maintenance cuff ( 120 ) from the vent position to the seal position, while the sterility maintenance cuff ( 120 ) relative to the syringe barrel ( 102 ) remains substantially stationary. A method of manufacturing a syringe system ( 100 ) containing a lyophilized drug, the method comprising: providing a syringe barrel ( 102 ), which has an open end ( 104 ) and a closed issue end ( 106 ) Has; the provision of a drug solution ( 112 ) in the syringe barrel ( 102 ); the introduction of a sterility maintenance cuff ( 120 ) in the syringe barrel ( 102 ), wherein the sterility maintenance cuff ( 120 ) a stopper ( 128 ) sealingly into the syringe barrel ( 102 ) engages a drug chamber ( 131 ) to determine; characterized by the provision of a ventilation passage ( 130 ) in the sterility maintenance cuff ( 120 ) through the plug ( 128 ); the insertion of a slip-on cap ( 150 ) in the Steri quality maintenance cuff ( 120 ) in a ventilation position, in which the ventilation passage ( 130 ) from the slip cap ( 150 ) is not cramped; then lyophilizing the drug solution ( 112 ); and the sealing of the ventilation passage ( 130 ) by moving the slip cap ( 150 ) in a sealing position in which the Aufsteckkappe ( 150 ) into the sterility maintenance cuff ( 120 ) and the ventilation passage ( 130 ) blocked. The method of claim 11, wherein the step of sealing the ventilation passage ( 130 ) the step of inserting an occlusive syringe ( 156 ) the Aufsteckkappe ( 150 ) in the ventilation passage ( 130 ). The method of claim 11, wherein the step of introducing the sterility maintenance cuff ( 120 ) in the syringe barrel ( 102 ) the complete introduction of the sterility maintenance cuff ( 120 ) in the syringe barrel ( 102 ) so that one end of the sterility maintenance cuff ( 120 ), opposite the plug end ( 128 ), within the syringe barrel ( 102 ) is located. The method of claim 11, wherein the plug end ( 128 ) of the sterility maintenance cuff ( 120 ) substantially in the same position in the syringe barrel ( 102 ) during the step of sealing the ventilation passage ( 130 ) is carried out.